CRF (chronic renal failure) is many primary and secondary nephropathys' end pathologic stage, which is caused by the nephron's necrobiosis and charactered by the kidney related abnormity of the excretory function, instability of the internal environment and endocrine disorder. It is a serous and refractory disease in the clinic and is one of the common diseases which affect the human's health and cause people to die. According to the statistic data of north America, west European and Australia, about 100˜50 persons one year in a million people develop to the stage of renal failure, what's more the number of the people who have developed to the stage of uremia is on a upward trend. The recent investigation in the America shows that in the past 10 yeas, the annul growth rate of the nephropathy patients in the final stage is reaching 9%, the incidence of the disease is beyond 200 person every one million, and this investigation forecasted that the total number of the uremia patients would exceed 250000 person. The related epidemiologic data of China indicated that the death rate of the CRF is 67.6 people every one million, and it is 10% of the total death rate. Though the dialysis and the renal transplantation are both the effective method, they can't prevent and cure the disease in the early and middle stage. What's more the expensive cost is a heavy duty to both the country and the family. In the world, there are only about 20% area owning the instrument of dialysis, and in China no more than 1.0% of the final-stage-nephropathy patients can receive the therapy of dialysis, and even less people have the chance to do the renal transplantation. According to this reality, it is a focus to study the non-dialysis therapy and medicine of the CRF in the field of the nephropathy therapeutired peony root.
In the recently years, the researcher of the whole world have finished a lot of studies on the mechanism of the rest nephron's necrobiosis. In the field of the non-dialysis therapy, they developed some medicines with clearly chemical structure and simple components, such as Ketosteril (some essential amino acid and keto acid), ACEI, active Vit D, EPO and etc. But all these medicines are hard to be widely used in China, because they are expensive and can only release some of the symptoms. ACEI can inhibit the remaining nephrons's fibrosis, but the individual variation is very big and there are many side-effection. The Chinese materia medica preparation “Mao shen kang pian” which reported effective to treat CRF in Chinese journals is individual component. Rhubarb is the principal drug in the “niao du qing chong ji”, and this Chinese patent medicine's main effect is eliminating the evil factors. The inventor believes that the mechanism of the CRF is the declination of “the primordial qi of the kidney” and the stasis of the mucous toxin. The declination of the “primordial qi of the kidney” means the declination of kidney-qi, kidney-yin and kidney-yang; the stasis of mucous toxin means that the metabolism waste produced by the body can't be discharged because of the declination of “the primordial qi of the kidney”. The declination of “the primordial qi of the kidney” is the principal reason the CRF, while the stasis of the mucous toxin is the main manifestation of the disease. Because of this mechanism, this disease's excessive manifestation is caused by the deficiency of the organs, and the deficiency-in-origin-and-excess-in-superficiality syndrome is usual seen. But by so far, there is not a drug that can protect the primordial of the kidney, balance the kidney-yin and kidney-yang, reinforce and reduce normally, strengthen the body resistance and discharge the mucous evil at the same time.
In a word, CRF is a serious and refractory clinical disease. Its incidence is on an upward trend and the related mortality has reached 10% of the total people's death rate. Because the cost of the dialysis and the transplantation is expensive while the kidney is difficult to get and the transplantation has so many complicating syndrome, dialysis and transplantation is difficult to be popularized. So that, developing the effective Chinese patent medicine on treating CRF is a worthy direction to be studied.
Technology Content
The purpose of this invention is to provide a medicine which can treat CRF and its preparation.
The purpose of this invention comes to the reality by the technical proposal as following:
The basic materials of the invented medicine are that:
Fleece-flower root100-600 part-by-weightdodder100-600 part-by-weightPseudostellaria root100-600 part-by-weightatractylodes rhizome100-600 part-by-weightWolfberry fruit100-600 part-by-weightAchyranthes root100-600 part-by-weight
The following herbs can be added into the basic materials:
Lycopus herb100-600 part-by-weightred peony root100-600 part-by-weightIndian bread100-600 part-by-weightalisma rhizome100-600 part-by-weightPsyllium seed100-600 part-by-weightrhubarb100-600 part-by-weight
The invented medicine can be prepared as following:
Take the prepared fleece flower root and the prepared rhubarb then crush them in to raw flour. According to the percolation recorded in the entry about fluidextract and extract, use 60%-90% alcohol as the dissolvent, soakage the raw flour then do the percolation, collect the percolate then retrieve the alcohol, condense to get the fluidextract; take atractylodes rhizome and crush it into raw flour, put the raw flour into the water 2-8 times of it for 2-8 hours, then distill the mixture to get the volatile oil from the vapor, keep the gruffs and the solution alone; dissolve the volatile oil into 60-90% alcohol then on the method of colloid mill grind the mixture to package the volatile oil. The ratio of volatile oil solution to β-dextrin is 1:4-10 and the ratio of β-dextrin and water is 1:1-3. After the grind, the mash is made, dehydrate the mash then crush it into powder. The powder is the volatile oil's clathrate; Cook the wolfberry fruit and indian bread in the water for 1-3 times and every time is 1-3 hours, the amount of the water is 6-10 times weight of the two herbs. Combine all the cooked water together then concentrate it, do the centrifugation to get the centrifugate; put the atractylodes rhizome's gruffs, solution and the rest of the herbs together, cook the mixture in the water for 1-3 times, each time is 1-2 hours and the water is 6-10 times weight of the mixture. Mingle all the cooked water and filtrate it. Concentrate the filtrated water then cool it down to the room temperature. Add alcohol to this solution until the alcohol's concentration up to 50-70%, standing the mixture to get the supernate solution. Retrieve the alcohol from the supernate solution and put the rest of it with the fluid extract (rhubarb, fleece-flower root) and the centrifuged extract (wolfberry fruit and fl), concentrate the mixture and dehydrate it in a low pressure, then crush the dry extract into fine powder. Mingle the fine powder, the volatile oil clathrate and the adjuvant together. The mixture can be made into many dosage forms needed in the clinic.
The fleece-flower root mentioned above can be exchanged by the prepared fleece-flower root. The atractylodes rhizome mentioned above can be exchanged by prepared atractylodes rhizome and the rhubarb can be exchanged by prepared rhubarb.
The identification method for quality control of the invented medicine (take the tablet for example) is that: crush 5 tablets into fine powder then dissolve the powder in the 30 ml chloroform and extract in the circumfluence for 1 hour. Filtrate the mixture. Distil the residue to dryness then dissolve it in 40 ml alcohol. Extract the solution in circumfluence for 1 hour, filtrate the solution and distil the filtrate to dryness. The residue dissolved to 1 ml in the alcohol is served as the solution for test. 1 g fleece-flower root is made into the control solution on the same way. Test the solutions by the thin layer chromatography. Imbibe 5 μl of the two kinds solutions and drop the solutions on the same silica gel G thin layer separately. Use aceticether-methanol-water (100:17:13) mixture as the developing agent and expand the two points at the stretch of 10 cm. Take the thin layer out and dry it in the air. Check the dehydrated lay under the 365 nm ultraviolet light and there should be the same fluorescent spot in the test chromatogram at same place of the control chromatogram; Take 4 piece of tablets and crush them into fine powder, then add 30 ml alcohol to the powder and distill the mixture in the circumfluence for 30 minutes. Filtrate the mixture to get the filtrated liquid and add 2 ml muriatic acid. After 1 hour abstraction in the circumfluence, concentrate the solution to 2 ml, then add 5 ml water and extract the new solution in 15 ml chloroform for 2 times. Distill the 30 ml chloroform to dry then get the dried extract. Add chloroform to solute the extract to 2 ml then get the test solution. Dissolve oleanolic acid into the methanol at the concentration of 1 mg/ml to get the control solution. According to the method of thin layer chromatography, imbibe the two solutions each 5 μl then drop them to the same silica gel G thin layer separately. Using chloroform-acetone (1:1) as the developing agent, expand the two points then take out the thin layer to dry in the air. Spray the 10% vitriolic-acid-alcohol solution to the thin layer, and then blow the thin layer with the hot air until the two points become clear. There should be the same color spot in the test solution's chromatogram at the same place of the control chromatogram; Dissolve 5 tablets in 30 ml methanol and extract in the circumfluent for 30 minutes. Filtrate the mixture and distill the filtrated liquid to dry. Collect the residue then dissolve it in 15 ml water. Extract the solution in the saturated n-butyl alcohol for 2 times on the condition of jerking. Each time the n-butyl alcohol is 15 ml. Mingle the two pieces of extracted liquid then distill the mixed liquid to dry. Dissolve the obtained residue in methanol to 1 ml to get the test solution. Prepare the paeoniflorin-methanol solution at the concentration of 1 mg/ml as the control solution. According to the method of thin layer chromatography, imbibe the two solutions each 5 μl then drop them to the same silica gel G thin layer separately. Using chloroform-ethylacetate-methanol-methanoic acid (40:5:10:0.2) as the developing agent, expand the two points then take out the thin layer to dry in the air. Spray the 10% vitriolic-acid-alcohol solution to the thin layer, and then blow the thin layer with the hot air until the two points become clear. There should be the same color spot in the test solution's chromatogram at the same place of the control chromatogram.
The content test method for quality control of the invented medicine is that: remove 10 tablets' clothing sheet, then weight them with accuracy. Crush these tablets to fine powder and weight out 1 g of the powder accurately. Put the powder into a 250 ml roundbottomed flask, then add 25 ml 2.5 mol/L sulfuric acid and 40 ml chloroform. After 4 hours of circumfluence, separate the chloroform layer. Add 40 ml chloroform to the rest solution and extract in the condition of circumfluence and waterbath for another 3 hours. Separate the chloroform layer and extract the rest solution with 10 ml chloroform for 3 times. Combinate all the chloroform then water-wash it to neutrality. Retrieve the chloroform and dissolve the residue into the methanol. Adjust this solution to 5 ml accurately to serve as the test solution. Prepare the emodin-methanol solution at the concentration of 0.1 mg/ml as the control solution. According to the method of thin layer chromatography (China pharmacopoeia version 1995 the No. 1 part supplement VIB), imbibe the test solutions 5 μl, the control solution 2 μl and 8 μl, then drop them to the same silica gel G thin layer separately. Using benzene-ethyl acetate-methanol-methanoic acid-water (3:1:0.2:0.05:0.5) as the developing agent, expand the 3 points at the stretch of 10 cm, then take out the thin layer to dry in the air. According to scan method of the thin layer chromatography (China pharmacopoeia version 1995 the No. 1 part supplement VIB), scan the chromatography at the wavelength: λS=435 nm, λR=600 nm. Measure and calculate the absorbance quantity of the test solution, then contrast it with the control solution and calculate to get the content of the test solution.
Each tablet must own no less than 0.07 mg emodin. Oral administration, 4 pieces of tablets one time, 3 times a day.